Mouse models of atherosclerosis provide an opportunity to examine the role of particular genes in[unreadable] lesion initiation and progression, but the data from different published studies are often difficult to[unreadable] compare. This is due to the use of different diets, analysis times (primarily very short times), sites of[unreadable] analysis, and the limitation of testing to a single mouse model. To address these problems, Core A[unreadable] will use the same protocols for all mouse studies, utilize a diet the mimics the Th1 inflammatory[unreadable] response observed in human disease, analyze multiple time points including very late stages of[unreadable] lesion development, and analyze 3 sites of lesion formation for all mice. It will centralize the[unreadable] generation and breeding of gene-knockout mice, and will perform bone-marrow transplants using[unreadable] these animals. The core laboratory has also recently developed a macrophage-specific retroviral[unreadable] vector that allows efficient transduction of hematopoietic stems cells that leads to gene expression[unreadable] in lesion macrophages in vivo. All of the projects in this PPG will utilize these approaches to perturb[unreadable] inflammatory genes and ask how these changes alter the initiation and progression of[unreadable] atherosclerotic lesions. The Core will also facilitate, coordinate and standardize sacrifice of all[unreadable] project study animals, prepare and blind tissue for analysis, provide histological stains and all[unreadable] quantitative methods of analysis. The combined analyses using identical protocols will allow direct[unreadable] comparison of the effects of perturbation of different inflammatory gene products, including[unreadable] inflammatory genes involved in the regulation of macrophage recruitment and activation and[unreadable] survival pathways.